The First Nations (Indigenous) people were the first settlers in the region, between 8,000 and 3,000 years ago. Traces of seasonal camps, characterized by arrowheads, scrapers, and other similar tools have been found. Ceramic objects dating from the Woodland period (3000 to 500 years ago) were also found, indicating that the region continued to be occupied by nomadic people during this period.

Upon the arrival of Samuel de Champlain in Quebec in 1608, this region was under the control of the Mohawks. France created an alliance through its missionaries with the Abenaki in Maine and Vermont. The French were driven to the valley of the St. Lawrence River near Trois-Rivières after a Mohawk victory in the war of 1660. The area around present-day Sherbrooke then became a battlefield between the two peoples who had to travel to the region, both of whom sought to obtain control of the territory. During the Seven Years' War between France and Britain, the Abenaki, still allied with the French, travelled along the rivers of the Eastern Townships, frequently near present-day Sherbrooke, during raids against British forts.

After the American Revolution, British Loyalists came from America to the region, and obtained government grants. The first attempts at colonization occurred in 1792 on the banks of the St. Francis River. This settlement was known as Cowan's Clearance. In 1793, loyalist Gilbert Hyatt, a farmer from Schenectady, New York, established his farm not far from the confluence of the Massawippi River and Coaticook River. Over the next two years, 18 families came to live on the site. The Crown acknowledged Hyatt's ownership of the land in 1801. Hyatt built the first dam on the Magog River, in collaboration with another loyalist named Jonathan Ball. Hyatt then built a gristmill in 1802 on the south bank of the river, effectively founding a small village that became known as "Hyatt's Mills". In 1818, the village was renamed after Governor General Sir John Sherbrooke at the time of his retirement and return to Britain.

Manufacturing activities were established that harnessed the Magog River's hydropower. In 1852 a railway line connected the cities of Montreal and Portland. From 1867 to 1892, the manufacturing system was based on hydraulic power. The founding of several important factories near the Gorges helped to attract more and more Francophone workers, coming mainly from the Beauce and elsewhere in Quebec.

Despite the town's English name and heritage, relatively few traces of the city's English past remain, and the vast majority of the city's residents speak French.

Sherbrooke has a humid continental climate, with long, cold, and snowy winters, warm summers, and short but crisp springs and autumns. Highs range from −5.8 °C (21.6 °F) in January to 24.6 °C (76.3 °F) in July. Annual snowfall is large, averaging at 287 centimetres (113 in), sometimes falling in May and October. Precipitation is not sparse any time of the year, but is the greatest in summer and fall and at its least from January to April, totalling 1,100 millimetres (43.3 in) annually.

• Limocar by Transdev, ☏ +1-819-562-8899, toll-free: +1-866-692-8899, sac@limocar.ca. Operates a daily bus route between Montreal and Sherbrooke with stops in Longueuil, Bromont, and Magog. Travel time to Sherbrooke from Montreal is 2-2.5 hours, from Longueuil is 2-2.25 hours, and from Magog is 30-50 minutes. (updated May 2022)
• Autobus La Québécoise, ☏ +1-418-872-5525, toll-free: +1-888-872-5525. Operates bus routes in southern Quebec. (updated May 2022) Routes operating to Sherbrooke:
  • From Quebec City to Sherbrooke with stops along the way including in Sainte-Foy and Victoriaville. Travel time from Quebec City is 3.75-4 hours and from Victoriaville is 1.5-1.75 hours. Operates daily.
  • From Quebec City to Sherbrooke with stops along the way only in Sainte-Foy and Drummondville. Travel time from Quebec City is 3.5 hours and from Drummondville is 1.25 hours. Operates two days per week.
  • From Trois-Rivières to Sherbrooke with stops along the way including in Drummondville. Travel time from Trois-Rivières is 2.25-2.5 hours and from Drummondville is 1.25 hour. Operates several days per week.

Many travellers to Sherbrooke use a ridesharing service: Kangaride/AmigoExpress and AllôStop offer rides from Montreal for about $10-20 plus a yearly membership fee of $7.50 for Kangaride (free 6 months trial account for students) or $7 for AllôStop. They also have rides to other major cities in Quebec and beyond and both offer free membership to students.

While there are no direct services between Sherbrooke and any US destinations, you may be able to find a ride with one of the above-mentioned ridesharing services.

• Kangaride
• AllôStop

From Trois-Rivières and points north: Take Autoroute 55 south to Autoroute 20. Continue on Autoroute 20 west until Exit 173. Take Autoroute 55 south until you get to Sherbrooke.

From Québec City and points east: Take Autoroute 20 until Exit 173. Then, turn onto Autoroute 55 south. Continue until you get to Sherbrooke.

From New England and points south: Take I-91 north until you hit the Canadian border. (Make sure you have your passport!) After the border, I-91 becomes Autoroute 55. Take Autoroute 55 north until you get to Sherbrooke.

From Montreal and points west: Drive onto Autoroute 10 east. Continue until you enter Sherbrooke (if you're past the east end of Autoroute 10, you've gone too far).

• Société de transport de Sherbrooke (STS), ☏ +1 819-566-1848, repartitionta@sts.qc.ca. Is the local transportation by bus, offers either a one trip 'jeton' that you have to buy beforehand at an authorized dealer for $3.25 giving you one trip with all transfers necessary or, more economically if you travel a lot, a day pass at $9.25 that either gives the right for one or two adults with children (age 12 or less) for a maximum of 6 passenger on one pass or one adult alone. Service for the bus ends at midnight. (updated Sep 2022)

About $30 for one end to the other of the city. From downtown to the farthest hotel would cost you $15.

• Taxis de Sherbrooke, ☏ +1 819-562-4717. (updated Aug 2022)

Also, if you have a cell phone anywhere in Quebec, try *TAXI: it will patch you in the taxi service of your region--the cost is 99¢.

• Uber. (updated Aug 2022)

Sherbrooke has many options for someone who enjoys nature.

• Bois Beckett. This forest is considered as being one of only two 'Ancient forests' in an urban area in the whole province. The forest's 8 trails have a total length of 6.1 km. 
• Marais Réal-D. Carbonneau. This wetland is home to many plants and animals, and makes for a delightful walk in spring, summer or fall. 

• Parc Lucien-Blanchard. Near the University of Sherbrooke, this park has trails for walking and cycling along the Magog river. During the summer there is a beach for free-water swimming and canoes and kayaks may be rented. There is also La Maison de l'Eau, an interpretation center featuring an exposition of various amphibians and fish.
• Parc Jacques-Cartier. This is a huge park where people come for different activities. The park is next to the Lac des Nations, and a walkway allows for pedestrians and cyclists to circle the lake. This is a very popular place during the summer.

• Siboire, 40, Boul. Jacques-Cartier South, ☏ +1 819-791-8440. Su-W 11:30-23:00, Th-Sa 11:30-00:00. A high-quality microbrewery and restaurant experience on the edge of Lac-des-Nations. Lunch and dinner menus. 
• Boquébière, 50 rue Wellington Nord. M Tu 17:00 to closing, W Sa 17:00-03:00, Th F 16:00-03:00, Su 19:00 to closing. Brew pub with snack menu, pizzas, hot dogs. 
• La Mare au Diable, 151 rue King Ouest, ☏ +1 819-562-1001. M-W 16:00-02:00, Th 11:00-02:00, F 11:00-03:00, Sa 16:00-03:00, Su 18:00-02:00. Brew pub with panoramic terrace. (updated Jan 2019)
• The Golden Lion (Le Lion d'Or), 2902 Rue College (Lennoxville). M-F 13:00, Sa 15:00-00:00. Come on Wednesday for "wing night," or any Thursday, Friday or Saturday night to party with the students of Bishop's University. (updated Jan 2019)

• Bar La Fakulté, 2155 rue King Ouest. La Fakulté is a huge student bar. It's only opened on Wednesdays but it's the biggest night in town. Be there early (22:00) unless you want to wait in a lineup. 
• Complexe le Living, 66 rue Meadow. Club with four rooms, each with a different setting. Hip-hop and techno. Good night on Friday only and some student Thursdays.