The BMC rider destroyed most of the field in the time trial to win by four seconds from Andrew Talansky (Garmin), with Tom Danielson (Garmin) third a further 58 seconds down.
Van Garderen is now one and a half minutes clear in the standings, with team-mate Mathias Frank second and Danielson third in the general classification.
The seven-stage race continues with a stage from Loveland to Fort Collins on Saturday before the finale in Denver on Sunday.
Stage five time trial results
1 Tejay van Garderen (USA) BMC Racing 25:01
2 Andrew Talansky (USA) Garmin +4
3 Tom Danielson (USA) Garmin +1:02
4 Steven Cummings (ENG) BMC Racing +1:04
5 Larry Warbasse (USA) BMC Racing +1:12
6 Tobias Ludvigsson (SWE) Argos +1:16
7 Kanstantsin Sivtsov (BLR) Team Sky +1:16
8 Lachlan Morton (AUS) Garmin +1:17
9 Christian Vande Velde (USA) Garmin +1:24
10 Mathias Frank (SUI) BMC Racing +1:26