The highways include the Trans-Canada and Yellowhead while some of the larger communities are Maple Creek, Kindersley, Kerrobert, and Unity.

[4] It originally continued west from Leader to Estuary and Empress, Alberta, before it turned north and followed Range Road 3293, adjacent to the Alberta–Saskatchewan border.

[5][7] In 1971, the Chesterfield Bridge across the South Saskatchewan River was opened, extending Highway 21 to Eatonia.

[10] The south end of Highway 21 begins at the Willow Creek Border Crossing.

From there, it heads north-west following Lodge Creek[11] for about 6 kilometres (3.7 mi) before turning north towards Govenlock.

Along this stretch, the highway crosses Battle Creek and provides access to the communities of Senate, Consul,[12] and Vidora.

[15] North of Leader, the highway crosses the South Saskatchewan River via the Chesterfield Bridge and heads in a northerly direction to Eatonia.

At Kerrobert, it turns into the town and has a 2.4-kilometre (1.5 mi) long concurrency with both Highways 51 and 31 before heading north.

[22] From south to north:[23] Media related to Saskatchewan Highway 21 at Wikimedia Commons