Route 143 is a north/south highway on the south shore of the Saint Lawrence River, in the Centre-du-Québec and Estrie regions of Quebec.

Its northern terminus is in Saint-François-du-Lac, at the junction of Route 132, and the southern terminus is in Stanstead, at the border with Vermont where the road continues past the Derby Line–Stanstead Border Crossing as U.S. Route 5 through Derby Line to New Haven, Connecticut.

Since Autoroute 55 closely parallels Route 143 for most of its length, much commercial traffic chooses the former.

However, it is a very busy route and takes much traffic from the border to the Sherbrooke local area.

Route 143 closely follows the Saint-François River between Sherbrooke and Ulverton.