This study compares the somatic genomic alterations in lung adenocarcinomas (ADCs) and lung squamous cell carcinomas (SqCCs) to identify novel drivers of lung carcinogenesis. The analysis includes exome sequences and copy number profiles from 660 ADCs and 484 SqCCs. Recurrent alterations in SqCCs were more similar to other squamous carcinomas than to ADCs. Novel significantly mutated genes included *PPP3CA*, *DOTL1*, and *FTSJD1* in ADCs, *RASA1* in SqCCs, and *KLF5*, *EP300*, and *CREBBP* in both tumor types. Novel amplification peaks included *MIR21* in ADCs, *MIR205* in SqCCs, and *MAPK1* in both. ADCs lacking receptor tyrosine kinase/Ras/Raf alterations revealed mutations in *SOS1*, *VAV1*, *RASA1*, and *ARHGAP35*. The study also identified neoantigen load, with 47% of ADCs and 53% of SqCCs having at least 5 predicted neoepitopes. While targeted therapies for ADCs and SqCCs are distinct, immunotherapies may be effective for both subtypes. The findings highlight the distinct somatic drivers of ADC and SqCC and suggest potential therapeutic strategies for each subtype.This study compares the somatic genomic alterations in lung adenocarcinomas (ADCs) and lung squamous cell carcinomas (SqCCs) to identify novel drivers of lung carcinogenesis. The analysis includes exome sequences and copy number profiles from 660 ADCs and 484 SqCCs. Recurrent alterations in SqCCs were more similar to other squamous carcinomas than to ADCs. Novel significantly mutated genes included *PPP3CA*, *DOTL1*, and *FTSJD1* in ADCs, *RASA1* in SqCCs, and *KLF5*, *EP300*, and *CREBBP* in both tumor types. Novel amplification peaks included *MIR21* in ADCs, *MIR205* in SqCCs, and *MAPK1* in both. ADCs lacking receptor tyrosine kinase/Ras/Raf alterations revealed mutations in *SOS1*, *VAV1*, *RASA1*, and *ARHGAP35*. The study also identified neoantigen load, with 47% of ADCs and 53% of SqCCs having at least 5 predicted neoepitopes. While targeted therapies for ADCs and SqCCs are distinct, immunotherapies may be effective for both subtypes. The findings highlight the distinct somatic drivers of ADC and SqCC and suggest potential therapeutic strategies for each subtype.