Talkeetna sits at the end of the 14-mile Talkeetna Spur Road, which branches off the Parks Highway at Mile 98.7. By car from Anchorage the drive takes about two and a half hours; from Fairbanks, allow around five hours south on the Parks Highway.
The Alaska Railroad is the scenic alternative. The Denali Star runs daily in summer between Anchorage and Fairbanks with a stop in Talkeetna -- around three hours from Anchorage. The train passes through backcountry that the highway bypasses and is worth the trip in its own right. In winter the Aurora Winter Train covers the same route on weekends.
There is no scheduled air service into Talkeetna Airport, but charter flights and air taxi services operate from it. If you are arriving as part of a flightseeing or mountaineering package, your operator will typically handle air transport from Anchorage.