Voters in at least six of 11 affected rural Colorado counties voted down a proposal Tuesday night to secede from the state.
Results were still being tallied in the five remaining counties that are part of the measure.
The goal of supporters was to discard edicts coming from Denver, the state capital, of gun control, green energy requirements and other Democrat-imposed measures.
No state has successfully seceded since West Virginia in 1863. If Tuesday's measure were to pass, the proposal will still need to get past state lawmakers and the U.S. Congress.
Ten of the counties are in the northeast of the state and one is in the northwest and would join Wyoming.
As the state has grown more urban, the rural counties pushing the secession movement have felt the Democrat-controlled Legislature has been ignoring their needs.
The passing of a strict gun-control law stoked anger and prompted the recall of two Democratic legislators in September.
Also in Colorado, voters passed a measure imposing taxes to pay for the costs associated with the dispensing of recreational marijuana, the Associated Press reported.
Proposition AA implements a 15% pot excise tax and 10% sales tax, which will be imposed in addition to a 2.9% sales tax imposed on marijuana retailers.
The sale of recreational pot became legal in Colorado on Jan. 1.
With six of 64 counties reporting, the marijuana initiative was passing 64.52% to 35.48%, according to the office of the Colorado Secretary of State.
Opponents of the measure said marijuana should be taxed similarly to beer, which has a lower tax rate, while supporters said the measure provides an opportunity to show the pot industry can be a boon to state finances.