The annual increase in the number of occupational accidents and diseases in the Palestinian manufacturing industries confirms a serious problem that threatens the Occupational Safety and Health (OSH) in such industries, with negative consequences in the society and economy. As the Palestinian OSH data are insufficient, tightwad, and with discrepancies in published data by different agencies, this study aimed to investigate the OSH status in the Palestinian manufacturing industries and determine the Palestinian OSH trends rates based on international practice in the EU and USA. Also, to shed light on the OSH situation in the manufacturing sector and warrant the inspection and monitoring of industries by the respective officials. The OSH data of 175 industrial establishments and 199 industrial employees was collected by meetings, interviews, and structured questionnaires for the period 2009–2016. The US and EU OSHA (Occupational Safety and Health Administration) formulas were used to calculate the OSH rates. The analysis showed that 32.30% of the industrial employees suffered from occupational injuries. The average injury rate was 7566 per 100,000 workers, indicating a low OSH level in the Palestinian manufacturing industries. The leather industry was found as the most dangerous in terms of OSH, with an average safety performance factor (SPF) of 145.6 off days/accident. Pearson’s chi-square test (χ2) revealed a correlation between occupational accidents and injuries and the employees’ commitment and lost working days. An OSH framework was developed based on safety and sustainable development pillars to assure effective enforcement of the OSH law and prevent future occupational accidents and diseases.