It runs northwest, from the junction of CentrePort Canada Way (PTH 190) and Sturgeon Road (near RM's boundary with the city of Winnipeg) to the community of Marquette, alongside the main Canadian Pacific Railway line.

PR 221 and the rail line share a grade-separated crossing at the Perimeter Highway (PTH 101).

[1] Between PTH 190 and the Perimeter Highway, PR 221 has been incorporated into the CentrePort Canada road network.

[2] Prior to the construction of CentrePort Canada Way, PR 221 linked with Inkster Boulevard (Winnipeg Route 25).

[3][4] Until the 1980s, PR 221 previously extended west of Marquette to PTH 26 along what is now Jubilee Road.