The southern end of I-225 begins at an interchange with Interstate 25, as a typical two lane interstate with a 65 mph speed limit. The road then traverses from the southern end northeastward through southern Denver, with Cherry Creek State Park and Cherry Creek Lake on its east side. After exits with DTC Boulevard and Yosemite Street in Greenwood Village, a large suburb of the Denver-Aurora Metropolitan Statistical Area, the road becomes three lanes with a fourth auxiliary lane traversing the Denver/Greenwood Village city limits. The highway interchanges with State Highway 83 at the northern boundary of Cherry Creek State Park. Following the exit at SH 83, the freeway enters a suburban area of Aurora, where it turns northward, narrowing back to two lanes and having a 55 mph speed limit, and has exits at Iliff Avenue, Mississippi Avenue, and Alameda Avenue, also signed as State Highway 30. After crossing Sand Creek, the freeway interchanges with Colfax Avenue, also signed as U.S. Highway 40, U.S. Highway 287 and Interstate 70 Business. After the exit, I-225 enters Adams County, continuing through the city of Aurora. The route then crosses a railroad and continues north, where it interchanges with Interstate 70. The northbound ramp to westbound I-70 reenters Denver, and the eastbound I-70 to southbound I-225 ramp originates in Denver but enters Aurora as it passes under the westbound I-70 to southbound I-225 ramp. The highway recently has gone under construction to widen to three lanes in each direction from Colfax to Mississippi, and later will be expanded from Mississippi to Parker, completing construction. The Colfax Avenue exit has also been reconstructed to include a 17th Place ramp for direct access to Anschutz Medical Campus.
Construction on I-225 began in May 1964 at Interstate 70. A section from Colfax Avenue to Sixth Avenue was opened in 1966. Five years later, a segment between Mississippi Avenue and Parker Road was opened, and construction began on another segment south of Parker Road, completed in May 1975. The rest of the route between Yosemite Street and Interstate 25 was completed in May 1976. Since completion of construction, the road has retained its original designation from I-25 to I-70.