K-99 connects Emporia with several smaller county seats to the south and north, including Sedan, Howard, Eureka, Alma, and Westmoreland while passing through the Flint Hills of eastern Kansas.

The highway passes through the western edge of the Chautauqua Hills immediately north of the Oklahoma state line.

cross Deer Creek to leave the city and diverge; the business route heads southwest to rejoin US-166, and K-99 curves north toward Elk County.

The two highways cross the North Fork of Wildcat Creek together before they diverge; US-166 heads east toward Elk Falls.

[5][7] K-99 crosses Salt Creek, which feeds the Fall River, and passes to the west and north of Severy, the latter side during the route's 1-mile-long (1.6 km) concurrency with east–west running US-400.

K-99 crosses the Fall River south of its junction with US-54 east of the county seat of Eureka.

The two highways head northeast and cross Bachelor Creek, which feeds the Verdigris River, before K-99 splits north.

K-99 enters the Emporia Downtown Historic District by crossing at grade the three-track BNSF Railway.

North of its intersection with US-50 (6th Avenue), the highway passes by the Granada Theater, the Lyon County History Center, and the Kress Building and east of the Keebler-Stone House.

K-99 turns west onto 12th Avenue and north onto Merchant Street to pass along the west side of the campus, which includes the Johnston Geology Museum, the Schmidt Museum of Natural History, and the National Teachers Hall of Fame.

At the north end of campus, the highway has a diamond interchange with I-35 and leaves the city of Emporia by crossing the Neosho River.

[5][7] K-99 continues north through the valley of the South Branch of Mill Creek, within which the highway does not follow section lines.

The highway has a grade crossing of the Union Pacific Railroad and curves north onto Missouri Street to pass through the Alma Downtown Historic District, which includes the Wabaunsee County Courthouse, the Wabaunsee County Historical Museum, and the Stuewe House.

South of the Brandt Hotel, K-99 turns east onto 7th Street and curves north to leave town as it approaches the railroad.

The highway follows Kansas Avenue through a grade crossing of a Union Pacific rail line to 2nd Street, onto which K-99 turns east to join K-9.

The two highways turn north one block east at Locust Street, which leads south to the Old Frankfort City Jail.

K-99 and K-9 pass the Frankfort School on their way out of town, and the two highways diverge 1 mile (1.6 km) north of the city limit.

The highway crosses Wolf Creek and intersects a Union Pacific rail line as the route enters the city from the south on Center Avenue and leaves to the east on Elm Street.

[12] In a November 6, 1936 resolution, K-11 was realigned from north of Louisville to south of Westmoreland, to eliminate five sharp curves.

In a December 22, 1993 resolution, KDOT approved and requested to realign US-166 south of Sedan, and to re-designate the former alignment as US-166 Business.

Also a segment from I-35 to K-170 was closed due to flooding from Dow Creek, which opened back up early the next day.

[27][28] In December 2020, a project began to reconstruct and realign a section of K-99, between two miles (3.2 km) north of I-70 and just south of K-18.