• A diagnosis of MF or post-ET or post-PV MF according to the 2016 World Health Organization (WHO) classification of MPN, confirmed by the most recent local pathology report.

• Measurable splenomegaly during the screening period as demonstrated by spleen volume of greater than equal to (\>=) 450 cubic square centimeter (cm\^3) by MRI or CT scan (results from MRI or CT imaging performed within 28 days prior to screening are acceptable).

• Participants with DIPSS risk category of intermediate-1 with symptoms, or intermediate-2, or high-risk.

• ECOG Performance Status less than or equal to (\<=) 2.

• Platelet count of 50 to less than (\<) 100 x 10\^9/L without platelet transfusion within 7 days prior to the first dose of selinexor.

• Absolute neutrophil count (ANC) \>=1.0 × 10\^9/L without need for growth factors within 7 days prior to the first dose of selinexor.

• Adequate liver function as defined by the following: aspartate transaminase (AST) and alanine aminotransferase (ALT) \<= 2.5 × upper limit normal (ULN) and serum total bilirubin \<= 3×ULN.

• Calculated creatinine clearance (CrCl) greater than (\>) 15 milliliter per minute (mL/min) based on the Cockcroft and Gault formula.

• Active symptoms of MF as determined by presence of at least 2 symptoms with a score \>= 3 or total score of \>= 10 at screening using the MFSAF V4.0.

• Participants must provide bone marrow biopsy samples (samples obtained up to 3 months prior to C1D1 are permitted) at screening and during the study.

• Participants currently not a candidate for stem cell transplantation.

• Participants must be willing to complete the MFSAF V4.0 daily during the study for evaluating the symptom response (i.e., TSS50).