The purpose of this study was to assess the influence of defining organizational purpose on the organizational performance of national health non-governmental organizations (NGOs) in Kenya. The study utilized positivism research philosophy and cross-sectional research design. The target population of the study was 564 chief executive officers (CEOs) and program directors of 282 national NGOs registered with the NGO coordination board. A sample size of 234 was selected using a random stratified sampling technique. Data collection was through a structured questionnaire while inferential and descriptive statistical techniques were used for data analysis. Structural equation modelling (SEM) was applied to test and explain the study hypothesis. Statistical package for social sciences (SPSS) Version 26 and Analysis of Moment Structures (AMOS) version 26 software were used for the analysis. The study findings determined that defining organizational purpose had a statistically significant positive influence on organizational performance of national health NGOs in Kenya (r squared = 0.41, beta = 0.642, CR = 7.534, p < 0.05). The study concludes that defining organizational purpose is vital for the organizational performance of national health NGOs in Kenya. The study hence recommends to the top management of national health NGOs in Kenya to clearly articulate the purpose of their organizations thus making employees and managers satisfied and committed to its achievement.