According to the U.S. Census Bureau, the county has a total area of 8,653 km² (3,341 mi²). 8,619 km² (3,328 mi²) of it is land and 35 km² (13 mi²) of it (0.40%) is water. As of the census² of 2000, there were 116,255 people, 45,823 households, and 31,572 families residing in the county. The population density was 13/km² (35/mi²). There were 48,427 housing units at an average density of 6/km² (15/mi²). The racial makeup of the county was 92.34% White, 0.46% Black or African American, 0.91% Native American, 0.53% Asian, 0.10% Pacific Islander, 3.67% from other races, and 1.99% from two or more races. 10.02% of the population were Hispanic or Latino of any race.

In the county the population was spread out with 25.00% under the age of 18, 9.40% from 18 to 24, 26.70% from 25 to 44, 23.70% from 45 to 64, and 15.20% who were 65 years of age or older. The median age was 38 years. For every 100 females there were 96.00 males. For every 100 females age 18 and over, there were 93.20 males.

The median income for a household in the county was $35,864, and the median income for a family was $43,009. Males had a median income of $32,316 versus $22,374 for females. The per capita income for the county was $18,715. About 7.00% of families and 10.20% of the population were below the poverty line, including 11.50% of those under age 18 and 8.10% of those age 65 or over.

Neighboring areas are the following: Garfield County, Pitkin County, Gunnison County, Delta County, Montrose County, San Juan County, Utah, and Grand County, Utah. Mesa County cities and towns are Clifton, Collbran, De Beque, Fruita, Fruitvale, Grand Junction, Orchard Mesa, Palisade, and Redlands.