This study focuses on the seismic stratigraphic analysis of the Nanuq South 3D seismic survey acquired over Nuiqsut, Central North Slope, Alaska to interpret the overall strata of the Ellesmerian, Beaufortian, and Brookian mega-sequences. Fourteen stratigraphic horizons were defined based on the seismic reflection patterns, and formation tops from the available well logs, and interpreted using a new semi-automatic horizon picking algorithm. The horizon tracking algorithm only needs interpreters manually picking 15% of the seismic vertical sections to generate horizons over the whole seismic survey. This result confirms that there is a significant decrease in interpretation effort with the automatic horizon picking algorithm.Four mega-sequences (Franklinian, Ellesmerian, Beaufortian, and Brookian) were identified based on interpreted horizons and well log tops. The thickness maps of mega-sequences were generated to analyze the depositional history and illustrate that four mega-sequences have different thickening directions. The Ellesmerian mega-sequence (Mississippian - Early Cretaceous) shows thickening northwestward with maximum thickness of 1.4 km. The Franklinian basement deepening towards the west caused Ellesmerian mega-sequence thickening in that direction. The Beaufortian (Early to Middle Jurassic and Early Cretaceous) and Brookian (Early Cretaceous to Cenozoic) mega-sequences both show thickening southwestward and the maximum thicknesses are 0.6 km and 2 km, respectively. The different thick patterns are believed related to the Brooks Range orogeny in the south, and the opening of the Canada Basin in the north during Jurassic–Early Cretaceous time. To further identify the potential reservoir, self-organizing map (SOM) was applied to multiple seismic attributes to analyze the seismic facies of Brookian mega-sequence. The results clearly highlight the west-east orientated incised valleys, moved sand to the basin floor fan delta in the southeast. Sand bodies along the shelf edge, slope, and basin floor could be a potential hydrocarbon production zone.