The 406 designation begins at East Main Street in Welland at a roundabout immediately west of East Main Street Tunnel beneath the Welland Canal. From here the now-four-lane divided road veers northeast and travels parallel to the canal. Two golf courses separate the canal. As the highway passes to the west of them, it jogs to the west and crosses a Trillium Railway spur (formerly at-grade, now over the railway), and meets Daimler Parkway and Woodlawn Road at a newly constructed interchange. Soon after, it crosses the Welland River and then the former channel of the canal, which was replaced by the current Welland By-Pass in the 1970s.