The thoroughfare begins at Huqingping Outer Ring Interchange near Hongqiao International Airport, where it meets S20 Outer Ring Expressway in Shanghai, and terminates at an interchange in Jiangbei District, where the highway joins G75 Lanzhou-Haikou Expressway.

It runs as a six-lane freeway to Jiamin Elevated Road, with a speed limit of 80 km/h (50 mph).

It runs roughly parallel to G318 in Shanghai, which was originally named Huqingping Highway (Chinese: 沪青平公路).

It intersects with G15W Changshu–Taizhou Expressway just west of the Beijing-Hangzhou Grand Canal and continues detouring Lake Tai to its south.

At Hongqiao Town to the southeast of Changxin County, G50 meets G25 Changchun-Shenzhen Expressway, and continues westbound until Jiepai Village, where it enters Anhui province.

G50 then splits with G4212 at a cloverleaf interchange northeast to Huaining County and heads southwest again, following the Yangtze River.

G50 concurs with most of G4201's southern tier and meets G4 Beijing–Hong Kong and Macau Expressway in Jiangxia District, Wuhan.

G50 then intersects with Hubei S13 Wuhan-Jianli Expressway and heads northwest to detour downtown Wuhan.

Four lanes of G50 are then carried across Yangtze River via Yichang Bridge and encounters Hubei S68 Fanba Expressway in Dianjun District.

From there, rugged landscape and mountainous terrain of southwestern Hubei necessitates the construction of numerous bridges and tunnels in Changyang Tujia Autonomous County and Enshi Tujia and Miao Autonomous Prefecture.